FDA cues up May verdict for Roche’s SMA challenger risdiplam

The FDA has started a priority review of Roche’s spinal muscular atrophy (SMA) candidate risdiplam, with a decision due by 24 May next year.

If approved, risdiplam will be the third drug to be approved for SMA after Biogen’s blockbuster antisense drug Spinraza (nusinersen) – which became the first drug to treat the muscle-wasting disease in 2016 – and Novartis’ one-shot gene therapy Zolgensma (onasemnogene abeparvovec) which got a green light from the FDA earlier this year.

Analysts at Jefferies have said they think risdiplam could become a $2 billion product at peak, despite the established competition, based on its clinical profile.

The regulatory filing in the US is based on results of the FIREFISH and SUNFISH phase 3 trials, which showed that Roche’s drug was able to slow down the progressive decline in muscle function that characterises the disease. The two studies recruited infants with type 1 SMA and older patients aged 2-25 with type 2 or 3 SMA, respectively.

Spinraza is viewed as risdiplam’s closest competitor if Roche’s drug is approved, as it addresses a similar age-range and both drugs require continuous dosing to exert their effects.

Risdiplam is an orally-active liquid taken once-daily, while Spinraza is given by intrathecal injection into the spine every four months after an initial loading period at days 1, 15, 30 and 60. Zolgensma in contrast is a one-off treatment used for children aged under 2 only.

Risdiplam’s eventual success will also depend on the price Roche sets for the drug if approved. Biogen’s drug costs $750,000 in the first year and $375,000 thereafter at US wholesale prices, while Zolgensma has a one-time cost of $1.2 million.

“If approved, risdiplam…would be the first at-home administered medicine for people living with SMA,” said Roche in a statement.

The company is also emphasising the safety of its oral therapy, saying that no treatment-related safety findings leading to study withdrawal have been seen in any risdiplam trial to date.

Roche has previously said it intends to file for approval of risdiplam in Europe a little later, in the first half of 2020.

Biogen reported sales of $547 million for Spinraza in the third quarter, the first since the launch of Zolgensma, and said the availability of Novartis’ gene therapy – which made $160 million in that period – hadn’t had a major impact on its product.

“As a reminder, Zolgensma is competing in a limited portion of the market, specifically the approximately 5% of SMA patients were under 2 years old,” commented Biogen’s chief financial officer Jeff Capello on the company’s third-quarter results call.

He conceded however that “within that segment, we have begun to see some impact on Spinraza performance.”

The looming approval of risdiplam could be a much tougher threat for Biogen, whose pipeline is looking thin following setbacks including the abandonment of Alzheimer’s candidate elenbecestat and idiopathic pulmonary fibrosis (IPF) drug STX-100 in the last few months.

It also abandoned another Alzheimer’s drug – aducanumab – before resurrecting the programme after a fresh look at the data, but that is still viewed as a very high-risk project.